Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer.

Tumor-associated macrophages (TAMs) exert profound influence over breast cancer progression, promoting immunosuppression, angiogenesis, and metastasis. Neuropilin-2 (NRP2), consisting of the NRP2a and NRP2b isoforms, is a co-receptor for heparin-binding growth factors including VEGF-C and Class 3 Semaphorins. Selective upregulation in response to environmental stimuli and independent signaling pathways endow the NRP2 isoforms with unique functionality, with NRP2b promoting increased Akt signaling receptor tyrosine kinases including VEGFRs, MET, and PDGFR.

Overcoming PD-1 Inhibitor Resistance with a Monoclonal Antibody to Secreted Frizzled-Related Protein 2 in Metastatic Osteosarcoma.

Secreted frizzled-related protein 2 (SFRP2) promotes the migration/invasion of metastatic osteosarcoma (OS) cells and tube formation by endothelial cells. However, its function on T-cells is unknown. We hypothesized that blocking SFRP2 with a humanized monoclonal antibody (hSFRP2 mAb) can restore immunity by reducing CD38 and PD-1 levels, ultimately overcoming resistance to PD-1 inhibitors.

Newly Identified Chemicals Preserve Mitochondrial Capacity and Decelerate Loss of Photoreceptor Cells in Murine Retinal Degeneration Models.

Metabolic stress and associated mitochondrial dysfunction are implicated in retinal degeneration irrespective of the underlying cause. We identified seven unique chemicals from a Chembridge DiverSET screen and tested their protection against photoreceptor cell death in cell- and animal-based approaches. Calcium overload (A23187) was triggered in 661W murine photoreceptor-derived cells, and changes in redox potential and real-time changes in cellular metabolism were assessed using the MTT and Seahorse Biosciences XF assay, respectively.

SAHA is neuroprotective in in vitro and in situ models of retinitis pigmentosa.

Purpose: Recent reports linking HDAC6 to mitochondrial turnover and neurodegeneration led us to hypothesize that an inhibitor such as Vorinostat (suberoylanilide hydroxamic acid, SAHA) may reduce mitochondrial damage found in retinitis pigmentosa (RP), a progressive neurodegenerative disease of the eye. Here we tested the efficacy of SAHA for its ability to protect photoreceptors in in-vitro and in-situ models of RP. As the stressor, we focused on calcium overload.